The Committee considered the foreshadowed inclusion of mitragynine and Mitragyna
speciosa in Schedule 9 of the SUSDP.

BACKGROUND

Mitragynine (also known as Kratom) is one of the alkaloids found in the leaves of the
South-East Asian tree Mitragyna speciosa, which is used extensively in Thailand to
increase work output and tolerance of direct sunlight. Mitragynine has psychoactive
properties and has been associated with being used as an opium substitute. Kratom
leaves are usually chewed, smoked or drunk as tea to achieve the desired affect.
Mitragyna speciosa is regulated in the same way as cocaine and heroin in Thailand and
carries the same restrictions and penalties as cocaine. There have also been reports of use
of mitragynine in Malaysia. Poisindex indicates that in adults, a dose of 50 mg of pure
mitragynine has produced motor excitement, rombergism, giddiness and tremors of the
face, extremities and tongue. In 1975, a study of 30 Thai Kratom users considered
chronic (more than 5 years use) noted that the leaves were chewed three times to 10 times
a day, with stimulant effects occurring after five minutes to 10 minutes.

The February 2003 Meeting considered preliminary information in relation to
mitragynine and Mitragyna speciosa. This consideration was initiated by an inquiry to
the TGA from an Australian resident wishing to import mitragynine and concern
regarding its potential for abuse. Members discussed the pharmacology and toxicology
of mitragynine, its potential for abuse, and the potential impact of its inclusion in the
SUSDP. The Committee agreed that there were grounds for inclusion of mitragynine and
Mitragyna speciosa in the SUSDP, based on mitragynine.s mode of action. To allow
appropriate public consultation, the Committee agreed to foreshadow the inclusion of
mitragynine and Mitragyna speciosa in Schedule 9 of the SUSDP, for consideration at
the June 2003 meeting.

The June 2003 Meeting noted the studies which showed that mitragynine exerted
agonistic effects on opioid receptors in in-vitro studies as well as an antinociceptive
action, which suggested that mitragynine has a morphine-like action on gastric acid
secretion. A member pointed out that tramadol is a mu-opioid receptor agonist included
in S4 and that it has a low potential for producing dependence. Members noted that the
information from Poisindex (Micromedex Healthcare) indicated that addiction and
withdrawal symptoms had occurred with chronic use of Mitragyna speciosa. The
Committee subsequently agreed to defer further consideration of the foreshadowed
decision on the view that additional information was required to better characterise the
physiological effects and mechanisms of action of mitragynine.

DISCUSSION

The Committee noted the advice received from XXXXXXXXXX stating that it had not
seen conclusive evidence relating to abuse or misuse of Mitragyna speciosa or
mitragynine. XXXXXXXXXX submitted that evidence on addiction and other harms
seen with Mitragyna speciosa or mitragynine had been largely anecdotal, and in some
instances contradictory. XXXXXXXXXX was of the view that given the range of
psychoactive substances being advertised on internet web sites, the limited user base and
the nature of use, it was unlikely that abuse of Mitragyna speciosa would become
widespread in Australia.

The Committee noted the literature review of pharmacological and toxicological data on
mitragynine prepared by the Secretariat. Animal experiments with mitragynine had
shown that it possessed pain threshold-elevating and antitussive properties. A series of
pharmacological studies in animal models, in vivo and in vitro, indicated that similar to
morphine, mitragynine and its derivatives produced central antinociception, inhibition of
intrinsic activity or electrically elicited guinea pig ileum contraction and drug-induced
gastric acid secretion, and inhibition of cAMP content. It was demonstrated in receptor
binding studies that these effects were mediated by opioid receptors and that further
studies also indicated that the pharmacological actions of mitragynine were selectively
blocked by antagonists for some sub-types of opioid receptors, predominantly mu- and
delta-receptor subtypes. (Matsumoto et al, Eur J Pharmacol 1996; Thongpradichote et al,
Life Sciences 1998; Tohda et al, Biological & Pharmaceutical Bulletin 1997; Tsuchiya et
al, Eur J Pharmacol 2002; Takayama et al, J Med Chem 2002; Yamanoto et al, General
Pharmacol 1999).

Based on available data, members noted that habitual users of mitragynine could develop
marked withdrawal syndromes, including hostility, aggression, rhinitis, inability to work,
excess tears, muscle and bone aches and jerky limb movement. Members concurred
with the view that there was a strong possibility of addiction if mitragynine was used in
doses high enough for mu-receptor crossover (1974-2003 Thomson Micromedex.
Micromedex(R) Healthcare Series Vol. 115) and agreed to restrict the use of the
substance.

Members discussed whether similar restrictions should be imposed on the plant species,
Mitragyna speciosa, in the light of reports that the leaves of the plant were being used for
smoking and chewing, and the leaf extracts drank as tea, to achieve the .desired. effects.
A member also raised the issue that there was a possibility that the plant was being used
for ornamental purposes and that the Committee should defer confirmation of the
foreshadowed decision to the next meeting to allow further information to be sought on
this matter.

DECISION 2003/39 – 23

The Committee agreed to take a pro-active approach and included mitragynine in
Schedule 9 of the SUSDP based on its potential for abuse. The Committee recognised
that whilst there were no widespread reports of abuse of mitragynine in Australia at this
time, the information relating to the use of mitragynine for psychoactive effects,
particularly in Asian countries, was well documented and easily found on the internet.

Schedule 9 – New Entry

MITRAGYNINE.

OUTCOME

The Committee agreed to consider the foreshadowed inclusion of the plant species,
Mitragyna speciosa, in S9 of the SUSDP at the February 2004 to seek additional
information on the plant's uses.